Michelangelo Scalone

Synthesis and Characterization of Iron–Nitrogen-Doped Graphene/Core–Shell Catalysts: Efficient Oxidative Dehydrogenation of N-Heterocycles

An important goal for nanocatalysis is the development of flexible and efficient methods for preparing active and stable core-shell catalysts. In this respect, we present the synthesis and characterization of iron oxides surrounded by nitrogen-doped-graphene shells immobilized on carbon support (labeled FeOx@NGr-C). Active catalytic materials are obtained in a simple, scalable and two-step method via pyrolysis of iron acetate and phenanthroline and subsequent selective leaching. The optimized FeOx@NGr-C catalyst showed high activity in oxidative dehydrogenations of several N-heterocycles. The utility of this benign methodology is demonstrated by the synthesis of pharmaceutically relevant quinolines. In addition, mechanistic studies prove that the reaction progresses via superoxide radical anions (·O2(-)).

Synthesis of (1S, 3aS)-8-(2,3,3a, 4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro [4.5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor agonist with anxiolytic-like properties

The development of 8-(2,3,3a,4,5, 6-hexahydro-1H-phenalen1-yl)-1-phenyl-1,3,8-triaza-spiro[4. 5]decan-4-ones 3 starting from (RS)-8-acenaphten-1-yl-1-phenyl-1,3, 8-triazaspiro[4.5]decan-4-one 1 is reported. The synthesis and the binding affinities at human OFQ and opioid (micro, kappa, delta) receptors of the stereoisomers 3a-f are described. In vitro the most selective compound, (1S,3aS)-8-(2,3,3a,4,5, 6-hexahydro-1H-phenalen1-yl)-1-phenyl-1,3,8-triaza-spiro[4. 5]decan-4-one 3c, was found to act as a full agonist at the OFQ receptor in the GTPgamma(35)S binding test. It turned out to be selective versus a variety of other neurotransmitter systems. When tested in vivo following intraperitoneal injection, compound 3c was found to decrease neophobia in a novel environment and to exhibit dose-dependent anxiolytic-like effects in the elevated plus-maze procedure, thus confirming the effects observed following intracerebroventricular infusion of the OFQ peptide in rat.

Substituted piperidines: Highly potent renin inhibitors due to induced fit adaptation of the active site

The identification, synthesis and activity of a novel class of piperidine renin inhibitors is presented. The most active compounds show activities in the picomolar range and are among the most potent renin inhibitors ever identified.

Synthesis of (R)- and (S)-4-hydroxyisophorone by ruthenium-catalyzed asymmetric transfer hydrogenation of ketoisophorone

Abstract The first synthesis of (R)- and (S)-4-hydroxyisophorone by catalytic transfer hydrogenation of ketoisophorone is reported. Ruthenium catalysts containing commercially available chiral amino alcohols afforded 4-hydroxyisophorone in up to 97% selectivity and 97% ee. (R)- or (S)-4-Hydroxyisophorones with >99% ee were isolated by crystallization. The catalyst precursors [RuCl2((S,R)-ADPE)(η6-p-cymene)] ((S,R)-ADPE=(1S,2R)-amino-1,2-diphenylethanol-N) and (RRu)-[RuCl((S,R)-ADPE−1)(η6-p-cymene)] (ADPE−1=amino-1,2-diphenylethanolato-N,O) were isolated for the first time and the X-ray crystal structure of the latter determined.

Highly Diastereo- and Enantioselective Synthesis of Monodifferentiated syn-1,2-Diol Derivatives through Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution

The first enantio- and diastereoselective approach to alpha-alkoxy-substituted syn-beta-hydroxyesters through highly efficient catalytic asymmetric transfer hydrogenation via dynamic kinetic resolution reactions from the corresponding racemic beta-ketoesters is described. In this atom-economical process, two contiguous stereogenic centers are generated simultaneously with an excellent diastereoselectivity (up to 99/1) and enantioselectivity (up to 99%), allowing a rapid access to a wide variety of aromatic and heteroaromatic monodifferentiated syn-1,2-diols.

New amidophosphine-phosphinites (tLANOPs) as chiral ligands for asymmetric hydrogenation reactions

Abstract The new amidophosphine-phosphinite (AMPP) ligands 4a–g (called tLANOP ligands) derived from the chiral hydroxy amide (R)- or (S)-2-hydroxy-3,3,N-trimethylbutyramide have been prepared in 48–83% yield. The crystal structures of the square planar complexes [(SP-4-3)-Pd((R)-dmphea)((S)-4a)]BF4 and [Rh((R)-4a)(COD)]BF4 have allowed the absolute configurations of the ligands to be assigned. In both complexes the 7-membered chelating ring of 4a has virtually the same twist-boat conformation. With this class of ligands the rhodium catalyzed asymmetric hydrogenation of 4-oxoisophorone enol acetate gave (S)-phorenol acetate in up to 71% ee. The iridium catalyzed asymmetric hydrogenation of the cyclic iminium salts 16a and 16b afforded after work-up the corresponding cyclic secondary amine (S)-17 in up to 86% ee, when bulky groups were present on the phenyl substituents on the two phosphorus atoms.

Synthesis of Nickel Nanoparticles with N-Doped Graphene Shells for Catalytic Reduction Reactions

The synthesis of novel nanoparticles is of general importance for the development of efficient heterogeneous catalysts. Herein, the preparation of carbon‐supported nickel‐based nanoparticles (NPs), modified by nitrogen‐doped graphene layers, is reported for the first time. The resulting materials were characterized in detail by TEM, X‐ray photoelectron spectroscopy (XPS), XRD, elemental analysis (EA), electron paramagnetic resonance (EPR), temperature‐programmed reduction (TPR), BET, and Raman analysis. Initial catalytic tests revealed the potential of this class of compounds in hydrogenation reactions.

Practical synthesis of (S)-2-(4-fluorophenyl)-3-methylbutanoic acid, key building block for the calcium antagonist Mibefradil

Abstract A short, technically feasible route was developed for the synthesis of (S)2-(4-fluorophenyl)-3-methylbutanoic acid (S)- 2 with an overall yield of 80% starting from 4-fluorophenylacetic acid. Asymmetric hydrogenation of the easily accessible unsaturated acid 3 in the presence of ruthenium(II) carboxylato complexes containing chiral atropisomeric diphosphines afforded (S)- 2 in up to 94% ee. The ee of (S)- 2 was upgraded to 98% by crystallization of its sodium salt. The same protocol was also applied to the synthesis of (S)-2-(4-chlorophenyl)-3-methylbutanoic acid.

Manganese(I)‐Catalyzed Enantioselective Hydrogenation of Ketones Using a Defined Chiral PNP Pincer Ligand

A new chiral manganese PNP pincer complex is described. The asymmetric hydrogenation of several prochiral ketones with molecular hydrogen in the presence of this complex proceeds under mild conditions (30-40 °C, 4 h, 30 bar H2 ). Besides high catalytic activity for aromatic substrates, aliphatic ketones are hydrogenated with remarkable selectivity (e.r. up to 92:8). DFT calculations support an outer sphere hydrogenation mechanism as well as the experimentally determined stereochemistry.

Efficient route to atropisomeric ligands--application to the synthesis of MeOBIPHEP analogues.

A highly efficient Pd-catalyzed P-C coupling reaction of easily accessible atropisomeric bisphosphane is described in the presence of various electron-poor aromatic iodides. The reactions are conducted in the presence of a Pd(II)/dppf catalyst in acetonitrile at 80 °C. The reaction conditions are compatible with several electron-withdrawing groups such as esters, cyano, chloro, and trifluoromethyl groups and lead to atropisomeric MeOBIPHEP derivatives in good to excellent yields and high enantiomeric purities.